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SARS-CoV-2 进入分子 ACE2、NRP1、TMPRSS2 和 FURIN 在雄性猕猴生殖组织中的表达。

Expression of SARS-CoV-2 entry molecules ACE2, NRP1, TMPRSS2, and FURIN in the reproductive tissues of male macaques.

机构信息

Department of Life Science, Kindai University, Higashiosaka, Osaka, 577-8502, Japan.

Faculty of Veterinary Medicine, Okayama University of Science, Imabari, Ehime, 794-8555, Japan.

出版信息

Histochem Cell Biol. 2024 Dec;162(6):465-475. doi: 10.1007/s00418-024-02314-9. Epub 2024 Aug 17.

Abstract

Coronavirus disease 2019 (COVID-19) reportedly affects male reproductive function by causing spermatogenesis dysfunction and suppressing testosterone secretion. However, the relationship between COVID-19 and impaired reproductive function, such as whether these effects on reproductive function are a direct effect of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection in male reproductive organs or an indirect effect of high fever, is not known. Here, we examined whether the cell entry molecules of SARS-CoV-2, namely, ACE2, NRP1, TMPRSS2, and FURIN, are expressed in the male reproductive organs using the testes and accessory gonads of macaques during the breeding season. RT-PCR expression analysis showed that the testes alone expressed all four molecules. Immunohistochemical staining of testis tissue sections revealed that ACE2 is expressed in Leydig cells and the apical region of Sertoli cells, whereas NRP1 is expressed in the cell bodies surrounding the Leydig and Sertoli cell nuclei. FURIN is mainly expressed in Leydig cells, secondary spermatocytes, and spermatids. However, TMPRSS2 immunopositive cells were not observed. Therefore, it was not possible to observe cells expressing all four molecules in the gonads and accessory gonads of male primates. These results suggest that SARS-CoV-2 is unlikely to directly affect spermatogenesis in primates or proliferate in cells of the seminiferous tubules and undergo release into the semen through the previously known ACE2-mediated infection route. However, the expression of three molecules, including ACE2, was observed in Leydig cells, suggesting that testosterone synthesis and secretion may be affected when primates, including humans, are infected with SARS-CoV-2.

摘要

据报道,2019 年冠状病毒病(COVID-19)通过导致生精功能障碍和抑制睾丸酮分泌而影响男性生殖功能。然而,COVID-19 与受损的生殖功能之间的关系,例如这些对生殖功能的影响是否是 SARS-CoV-2 在男性生殖器官中的直接感染作用,或者是否是高热的间接作用,尚不清楚。在这里,我们检查了 SARS-CoV-2 的细胞进入分子,即 ACE2、NRP1、TMPRSS2 和 FURIN,是否在繁殖季节的猕猴睾丸和附属性腺中表达。RT-PCR 表达分析显示,睾丸单独表达了这四种分子。睾丸组织切片的免疫组织化学染色显示,ACE2 在 Leydig 细胞和 Sertoli 细胞的顶端区域表达,而 NRP1 在围绕 Leydig 和 Sertoli 细胞核的细胞体中表达。FURIN 主要在 Leydig 细胞、次级精母细胞和精子细胞中表达。然而,没有观察到 TMPRSS2 免疫阳性细胞。因此,在雄性灵长类动物的性腺和附属性腺中,不可能观察到表达所有四种分子的细胞。这些结果表明,SARS-CoV-2 不太可能直接影响灵长类动物的精子发生,也不可能通过先前已知的 ACE2 介导的感染途径在生精小管的细胞中增殖并释放到精液中。然而,在 Leydig 细胞中观察到三种分子(包括 ACE2)的表达,表明当包括人类在内的灵长类动物感染 SARS-CoV-2 时,睾丸酮的合成和分泌可能会受到影响。

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